In animals, inherited and progressive retinal diseases are commonly referred to as progressive retinal atrophy (PRA), and are characterised by progressive retinal degeneration resulting in loss of vision. In typical PRA, rod photoreceptor responses are lost first followed by cone photoreceptor responses [1]. Fundus changes observed in PRA are bilateral and symmetrical and include tapetal hyper-reflectivity in the early stages followed by vascular attenuation, pigmentary changes and atrophy of the optic nerve head in the later stages of disease [2]. Numerous forms of PRA have been documented in more than 100 dog breeds and while they exhibit similar clinical signs, the aetiology, age of onset and rate of progression vary between and within breeds. Several disease-causing genes have been reported for some forms of PRA [3], but many remain undefined.
PRA is considered the veterinary equivalent of Retinitis Pigmentosa (RP), which is the collective name for a group of inherited human retinal disorders that leads to progressive loss of vision in approximately 1 in 4000 people [4,5,6]. Rod photoreceptor cells are predominantly affected and therefore clinical symptoms typically include night blindness and loss of peripheral vision. With disease progression the cones also degenerate resulting in central vision loss and eventually complete blindness is possible. To date, 182 genes have been shown to cause a wide spectrum of retinal disease, including RP (RetNet; www.sph.uth.tmc.edu/retnet/). Mutations in these genes currently only account for approximately 30% of recessive RP cases. [7].
Canine diseases have already proved valuable natural models for the study of many varied human conditions such as cardiac conotruncal malformations [8], myotubular myopathy [9] and hereditary retinopathies such as Leber congenital amaurosis and achromatopsia [10,11]. Further to this, canine models for human eye diseases have proved invaluable in gene-therapy studies, most notably the canine model of Leber congenital amaurosis associated with RPE65 [12,13,14,15,16].
Most PRA cases in the Golden Retriever (GR) are clinically indistinguishable from other forms of PRA. The mode of inheritance appears from pedigree information to be autosomal recessive and the age of diagnosis is most commonly at a relatively late age of approximately 6 years.
There is therefore a great need to identify the causal genetic variant responsible for PRA in canines.